2,2,2-Trifluoro-1-methoxyethanol → HCID 25018656, compound

HRID 912997Notes

Reaction equation

[OH:1][C:2]1[C:3](=[O:10])[CH:4]=[C:5]([CH3:9])[N:6]([CH3:8])[CH:7]=1.C[O:12][CH:13](O)[C:14]([F:17])([F:16])[F:15].C([O-])([O-])=O.[K+].[K+]>>[OH:1][C:2]1[C:3](=[O:10])[CH:4]=[C:5]([CH3:9])[N:6]([CH3:8])[C:7]=1[CH:13]([OH:12])[C:14]([F:17])([F:16])[F:15]

Participants

Reactant 3

HCID 98922,2,2-Trifluoro-1-methoxyethanol

HCID 11430Potassium Carbonate

HCID 12280547HCID 12280547, compound

Product 1

HCID 25018656HCID 25018656, compoundYield 39%

Conditions

Temperature: 130 °C

Procedure

A mixture of 5-hydroxy-1,2-dimethyl-1H-pyridin-4-one (9.40 g, 67.6 mmol), trifluoroacetaldehyde methyl hemiacetal (28 mL) and K2CO3 (1.40 g, 10.0 mmol) was sealed in a parallel reactor and stirred overnight at 130° C. The reaction mixture was evaporated to dryness, and the residue was purified by flash column chromatography using a mixture of i-PrOH and a 28-30% conc. NH4OH solution (70/30, v/v) as eluant. Fractions containing pure product were pooled together, and evaporated to give the title compound as a light orange powder (6.3 g, 39% yield). HPLC purity (peak area percent) of this compound is 99.8% at λ=254 nm using HPLC Method 2 as described above. 1H NMR (400 MHz, DMSO-D6) δ: 6.83 (br s, 2H, 20H), 6.21 (s, 1H), 5.88 (q, J=8.7 Hz, 1H), 3.73 (s, 3H, NCH3), 2.31 (s, 3H, CH3); MS m/z 238.1 [M+1]+, 220.2, 192.3, 172.3 (100%). A second less pure fraction of the title compound (7.0 g) was also obtained, and was used without further purification in step 1 of Example 14 below.

Workup

customwas sealed in a parallel reactor
customThe reaction mixture was evaporated to dryness
customthe residue was purified by flash column chromatography
additiona mixture of i-PrOH
additionFractions containing pure product
customevaporated

Sources & evidence

ORD record: ord-9e42f2a06b8f4dcea9bf67d16211d455
Source dataset: uspto-grants-2011_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08026261B2

Reaction notes

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